The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats.
The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats.
复制标题
DOI：
10.1007/s00213-020-05648-z
复制
发表时间：
2020-12
影响因子：
3.4
通讯作者：
Baumann MH
中科院分区：
文献类型：
--
作者：
Brandt SD;Walters HM;Partilla JS;Blough BE;Kavanagh PV;Baumann MH
新型精神活性物质（NPS）的非医疗用途是一个全球性的公共卫生问题。所谓的“苯并呋喃”化合物，5-(2-氨基丙基)苯并呋喃 (5-APB) 和 6-(2-氨基丙基)苯并呋喃 (6-APB)，是对人类使用者具有类似兴奋剂特性的 NPS。已知这些物质与转染细胞中的单胺转运蛋白和 5-HT 受体相互作用，但对其在动物模型中的作用知之甚少。在这里，我们在大鼠脑突触体中使用体外单胺转运蛋白测定来表征 5-APB 和 6-APB 及其 N-甲基衍生物 5-MAPB 和 6-MAPB 与 3,4-亚甲二氧基苯丙胺 (MDA) 和 3,4-亚甲二氧基甲基苯丙胺 (MDMA) 的影响。使用微透析取样对清醒雄性大鼠的伏核进行比较，评估 5-APB（0.3 和 1.0 mg/kg，静脉注射）和 6-APB（0.3 和 1.0 mg/kg，静脉注射）与 MDA（1.0 和 3.0 mg/kg，静脉注射）的体内神经化学和行为影响。所有四种苯并呋喃衍生物都是多巴胺转运蛋白 (DAT)、去甲肾上腺素转运蛋白 (NET) 和血清素转运蛋白 (SERT) 的底物型释放剂，具有纳摩尔效力，类似于 MDA 和 MDMA 产生的效果。然而，苯并呋喃在引发转运蛋白介导的释放方面比 MDA 和 MDMA 至少强 3 倍。与 MDA 一样，两种苯并呋喃都会引起大脑中细胞外多巴胺和血清素的剂量相关升高，但苯并呋喃比 MDA 更有效。苯并呋喃衍生物还诱导了深刻的行为激活，其特征是注射后持续至少 2 小时的向前运动。总体而言，苯并呋喃在体外和体内都比 MDA 更有效，可在大鼠中产生持续的兴奋剂样作用。这些数据表明，苯并呋喃类化合物可能具有滥用倾向，并可能带来不良反应的风险，特别是与滥用药物或增强大脑中单胺传输的药物一起使用时。
The non-medical use of new psychoactive substances (NPS) is a worldwide public health concern. The so-called “benzofury” compounds, 5-(2-aminopropyl)benzofuran (5-APB) and 6-(2-aminopropyl)benzofuran (6-APB), are NPS with stimulant-like properties in human users. These substances are known to interact with monoamine transporters and 5-HT receptors in transfected cells, but less is known about their effects in animal models. Here, we used in vitro monoamine transporter assays in rat brain synaptosomes to characterize the effects of 5-APB and 6-APB, together with their N-methyl derivatives 5-MAPB and 6-MAPB, in comparison to 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA). In vivo neurochemical and behavioral effects of 5-APB (0.3 and 1.0 mg/kg, i.v.) and 6-APB (0.3 and 1.0 mg/kg, i.v.) were assessed in comparison to MDA (1.0 and 3.0 mg/kg, i.v.) using microdialysis sampling in the nucleus accumbens of conscious male rats. All four benzofuran derivatives were substrate-type releasers at dopamine transporters (DAT), norepinephrine transporters (NET) and serotonin transporters (SERT) with nanomolar potencies, similar to the profile of effects produced by MDA and MDMA. However, the benzofurans were at least 3-fold more potent than MDA and MDMA at evoking transporter-mediated release. Like MDA, both benzofurans induced dose-related elevations in extracellular dopamine and serotonin in the brain, but benzofurans were more potent than MDA. The benzofuran derivatives also induced profound behavioral activation characterized by forward locomotion which lasted for at least 2 h post-injection. Overall, benzofurans are more potent than MDA in vitro and in vivo, producing sustained stimulant-like effects in rats. These data suggest that benzofuran-type compounds may have abuse liability, and could pose risks for adverse effects, especially if used in conjunction with abused drugs or medications which enhance monoamine transmission in the brain.
登录
查看更多内容
影响因子：
2.9
作者：
Daveluy, Amelie;Geniaux, Helene;Haramburu, Francoise
通讯作者：
Haramburu, Francoise
影响因子：
4.2
作者：
Dolan, Sean B.;Forster, Michael J.;Gatch, Michael B.
通讯作者：
Gatch, Michael B.
DOI：
10.1124/jpet.110.176271
发表时间：
2011-04-01
影响因子：
3.5
作者：
Baumann, Michael H.;Clark, Robert D.;Rothman, Richard B.
通讯作者：
Rothman, Richard B.
影响因子：
2.2
作者：
Adamowicz, Piotr;Zuba, Dariusz;Byrska, Bogumila
通讯作者：
Byrska, Bogumila
影响因子：
3.6
作者：
Cha, Hye Jin;Lee, Kwang-Wook;Kim, Hyung Soo
通讯作者：
Kim, Hyung Soo